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. 2023 Sep 28;20(1):37.
doi: 10.1186/s12989-023-00547-5.

Difference in carcinogenicities of two different vapor grown carbon fibers with different physicochemical characteristics induced by intratracheal instillation in rats

Kei Sato  1 , Hiroko Fukui  2 , Yuji Hagiwara  2 , Ryoji Ogawa  2 , Ayako Nishioka  2 , Takamasa Numano  3 , Taiki Sugiyama  3 , Mayumi Kawabe  3 , Yukinori Mera  3 , Tadashi Yoneda  2
Affiliations

Difference in carcinogenicities of two different vapor grown carbon fibers with different physicochemical characteristics induced by intratracheal instillation in rats

Kei Sato et al. Part Fibre Toxicol. .

Abstract

Background: Carbon fibers are high aspect ratio structures with diameters on the submicron scale. Vapor grown carbon fibers are contained within multi-walled carbon tubes, with VGCF™-H commonly applied as a conductive additive in lithium-ion batteries. However, several multi-walled carbon fibers, including MWNT-7, have been reported to induce lung carcinogenicity in rats. This study investigated the carcinogenic potential of VGCF™-H fibers in F344 rats of both sexes with the vapor grown carbon fibers VGCF™-H and MWNT-7 over 2 years. The carbon fibers were administered to rats by intratracheal instillation at doses of 0, 0.016, 0.08, and 0.4 mg/kg (total doses of 0, 0.128, 0.64, and 3.2 mg/kg) once per week for eight weeks and the rats were observed for up to 2 years after the first instillation.

Results: Histopathological examination showed the induction of malignant mesothelioma on the pleural cavity with dose-dependent increases observed at 0, 0.128, 0.64, and 3.2 mg/kg in rats of both sexes that were exposed to MWNT-7. On the other hand, only two cases of pleural malignant mesothelioma were observed in the VGCF™-H groups; both rats that received 3.2 mg/kg in male. The animals in the MWNT-7 groups either died or became moribund earlier than those in the VGCF™-H groups, which is thought related to the development of malignant mesothelioma. The survival rates were higher in the VGCF™-H group, and more carbon fibers were observed in the pleural lavage fluid (PLF) of the MWNT-7 groups. These results suggest that malignant mesothelioma is related to the transfer of carbon fibers into the pleural cavity.

Conclusions: The intratracheal instillation of MWNT-7 clearly led to carcinogenicity in both male and female rats at all doses. The equivocal evidence for carcinogenic potential that was observed in male rats exposed to VGCF™-H was not seen in the females. The differences in the carcinogenicities of the two types of carbon fibers are thought due to differences in the number of carbon fibers reaching the pleural cavity. The results indicate that the carcinogenic activity of VGCF™-H is lower than that of MWNT-7.

Keywords: 2-Year carcinogenicity study; Carbon fiber; Intratracheal instillation; Mesothelioma; Multi-walled carbon nanotube; Rat; Vapor grown carbon fiber.

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Conflict of interest statement

K.S., H.F., Y.H., R.O., A.N., T.Y. are employees of the sponsor of this study. T.N., T.S., M.K., Y.M. are employees of DIMS Institute of Medical Sciences Inc. However, this did not influence the objectivity of the study. The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Representative scanning electron microscopic images of MWNT-7 (A) and VGCF™-H (B) fibers in the prepared solution. VGCF™-H fibers were shorter and thicker than MWNT-7 fibers. The scale bar indicates 1 μm
Fig. 2
Fig. 2
Kaplan–Meier survival plot for the male rats in the nontreatment, control, MWNT-7, and VGCF™-H groups in each dose
Fig. 3
Fig. 3
Kaplan–Meier survival plot for the female rats in the nontreatment, control, MWNT-7, and VGCF™-H groups in each dose
Fig. 4
Fig. 4
Representative gross pathological image of thoracic area in the male MWNT-7 group that died at week 45 of the experimental period (A) and an image of the male VGCF™-H group that died at week 60 of the experimental period (B). The small white granules (yellow arrows) and white nodule (green arrows) had spread around the lungs, and reached the heart epicardium, diaphragm, and thoracic wall (A). The white nodule (green arrows) and the swelling (red arrows) present around the lungs and heart (B). The scale bar indicates 10 mm
Fig. 5
Fig. 5
Representative histological images of the lung and heart in the MWNT-7 and VGCF™-H group. Deposition of MWNT-7 fibers (arrow in A) and the alveolar hyperplasia (A). B, C indicates the malignant mesothelioma in the MWNT-7 group. It indicates the deposition of VGCF™-H fibers (arrow in D) in the lung (D). E, F indicates the malignant mesothelioma in the VGCF™-H group. The scale bar indicates 50 μm
Fig. 6
Fig. 6
Correlation between surface area at total doses and the incidence of the malignant mesothelioma. The total dose of 0.128, 0.64, 3.2 mg/kg were a surface area of 0.0032, 0.016, and 0.08 m2/kg for MWNT-7, a surface area of 0.00192, 0.0096, and 0.048 m2/kg for VGCF™-H
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